Interaction of Nontypable Haemophilus influenzae with Human Respiratory Mucosa In Vitro

Read, Robert C.; Wilson, Robert; Rutman, A; Lund, Valerie J.; Todd, Howard; Brain, Anthony P.R.; Jeffery, Peter K.; Cole, Peter

doi:10.1093/infdis/163.3.549

Cited by 145 publications

(150 citation statements)

References 35 publications

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“…If the bacteria manage to overcome the mucociliary escalator, they may colonize and cause damage to the epithelial cells and breakdown of tight junctions (5,6). Consequently, the bacteria reach the basement membrane and the extracellular matrix (ECM), and may penetrate into deeper tissue layers and consequently into the circulation.…”

mentioning

confidence: 99%

Haemophilus influenzae Surface Fibrils Contribute to Serum Resistance by Interacting with Vitronectin

Hallström

Trajkovska

Forsgren

et al. 2006

The Journal of Immunology

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Vitronectin inhibits the membrane attack complex of the complement system and is found both in plasma and the extracellular matrix. In this study, we have identified the outer membrane protein Haemophilus surface fibrils (Hsf) as the major vitronectin-binding protein in encapsulated H. influenzae type b. A H. influenzae mutant devoid of Hsf showed a significantly decreased binding to both soluble and immobilized vitronectin as compared with the wild-type counterpart. Moreover, Escherichia coli-expressing Hsf at the surface strongly adhered to immobilized vitronectin. Importantly, the H. influenzae Hsf mutant had a markedly reduced survival as compared with the wild-type bacterium when incubated with normal human serum. A series of truncated Hsf fragments were recombinantly manufactured in E. coli. The vitronectin binding regions were located within two separate binding domains. In conclusion, Hsf interacts with vitronectin and thereby inhibits the complement-mediated bactericidal activity, and thus is a major H. influenzae virulence factor.

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mentioning

confidence: 99%

Haemophilus influenzae Surface Fibrils Contribute to Serum Resistance by Interacting with Vitronectin

Hallström

Trajkovska

Forsgren

et al. 2006

The Journal of Immunology

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“…Adherence of Rd/wt-Hap to fibronectin and collagen IV was even more impressive than adherence to epithelial cells, suggesting that Hap may serve primarily to facilitate H. influenzae adherence to extracellular matrix proteins. Along these lines, it is noteworthy that H. influenzae associates preferentially with damaged epithelium and exposed basement membrane in experiments with nasopharyngeal tissue in organ culture (12).…”

Section: Discussionmentioning

confidence: 96%

Chromosomal Expression of the Haemophilus influenzae Hap Autotransporter Allows Fine-Tuned Regulation of Adhesive Potential via Inhibition of Intermolecular Autoproteolysis

Fink

Geme

2003

J Bacteriol

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The Haemophilus influenzae Hap autotransporter is a nonpilus adhesin that promotes adherence to respiratory epithelial cells and selected extracellular matrix proteins and facilitates bacterial aggregation and microcolony formation. Hap consists of a 45-kDa outer membrane translocator domain called Hap ␤ and a 110-kDa extracellular passenger domain called Hap S . All adhesive activity resides within Hap S , which also contains protease activity and directs its own secretion from the bacterial cell surface via intermolecular autoproteolysis. In the present study, we sought to determine the relationship between the magnitude of Hap expression, the efficiency of Hap autoproteolysis, and the level of Hap-mediated adherence and aggregation. We found that a minimum threshold of Hap precursor was required for autoproteolysis and that this threshold approximated expression of Hap from a chromosomal allele, as occurs in H. influenzae clinical isolates. Chromosomal expression of wild-type Hap was sufficient to promote significant adherence to epithelial cells and extracellular matrix proteins, and adherence was enhanced substantially by inhibition of autoproteolysis. In contrast, chromosomal expression of Hap was sufficient to promote bacterial aggregation only when autoproteolysis was inhibited, indicating that the threshold for Hap-mediated aggregation is above the threshold for autoproteolysis. These results highlight the critical role of autoproteolysis and an intermolecular mechanism of cleavage in controlling the diverse adhesive activities of Hap.Most bacterial diseases begin with colonization of a particular mucosal surface. Successful colonization requires that bacteria overcome mechanical cleansing and evade the local immune response. A number of specific mechanisms exist to achieve these goals, including the expression of surface-exposed proteins called adhesins, which bind to receptors on the host epithelial surface, and the formation of structured communities called biofilms, which resist mechanical, chemical, and immunological attack (20).Nontypeable Haemophilus influenzae is a nonencapsulated, gram-negative bacterium that commonly causes human respiratory tract disease, including otitis media, sinusitis, bronchitis, and pneumonia (19). Infection by nontypeable H. influenzae begins with colonization of the nasopharynx (10). In most individuals, colonization persists for weeks to months without symptoms. However, under certain circumstances bacteria spread contiguously to the middle ear, the sinuses, or the lungs, resulting in disease. Studies of tympanostomy tubes from patients with recurrent otitis media and examination of experimentally infected chinchillas suggest that biofilm formation may represent an important mechanism of persistence by nontypeable H. influenzae (3, 11).To facilitate colonization, H. influenzae elaborates both pilus and nonpilus adhesins. The Hap protein is a nonpilus adhesin that was first identified based on its ability to promote intimate interaction with cultured epithelial cells ...

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“…READ et al [23] have hypothesized that, in individuals whose primary airway defences are compromised (i.e. impaired mucociliary clearance and increased mucus production), a "vicious circle of events" results in chronic airway inflammation and damage as a consequence of the host-mediated response to bacterial infections.…”

Section: The Putative Mechanisms Of Bacterial-induced Chronic Airway mentioning

confidence: 99%

Bacterial-induced release of inflammatory mediators by bronchial epithelial cells

Khair¹,

Davies²,

Devalia³

1996

Eur Respir J

165

118

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Interaction of Nontypable Haemophilus influenzae with Human Respiratory Mucosa In Vitro

Cited by 145 publications

References 35 publications

Haemophilus influenzae Surface Fibrils Contribute to Serum Resistance by Interacting with Vitronectin

Haemophilus influenzae Surface Fibrils Contribute to Serum Resistance by Interacting with Vitronectin

Chromosomal Expression of the Haemophilus influenzae Hap Autotransporter Allows Fine-Tuned Regulation of Adhesive Potential via Inhibition of Intermolecular Autoproteolysis

Bacterial-induced release of inflammatory mediators by bronchial epithelial cells

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